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Title:Engineering yeast to synthesize high-value natural products from plant cell wall
Author(s):Sun, Liang
Director of Research:Jin, Yong-Su
Doctoral Committee Chair(s):Miller, Michael J.
Doctoral Committee Member(s):Rao, Christopher V; Erdman, John W
Department / Program:Food Science & Human Nutrition
Discipline:Food Science & Human Nutrition
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Yeast Saccharomyces cerevisiae, Metabolic engineering, Lignocellulose biomass, Hemicellulose, Xylose, Xylodextrin, Acetate, Acetyl-CoA, Natural products, β-carotene, Vitamin A, Triacetic acid lactone
Abstract:Second-generation bioenergy and biorefineries based on ligonocellulosic plant materials offers a promising solution to address global concerns about limited natural resources and climate change. Economically feasible production of biofuels and chemicals from plant biomass requires complete and efficient bioconversion of cellulosic substrates. However, none of the industrially preferred microorganisms is capable of fermenting cellulosic carbon economically. Besides, the presence of acetic acid in cellulosic hydrolysate hampered the yields of target products. In addition, product range of existing microbial yeast factories is far from enough to compete with the vetted petroleum-based refineries and chemical synthesis. The overall goal of this thesis study is to develop metabolically engineered yeast platforms and novel strategies for diversifying product range, detoxifying acetic acid, and expanding substrate utilization of plant biomass hydrolysates. First, the respiratory nature of xylose metabolism in engineered Saccharomyces cerevisiae was explored and harnessed for high-level production of β-carotene. Subsequently, we illustrated efficient conversion of xylose-enriched biosorghum hydrolysates into β-carotene by this engineered strain. Next, vitamin A production was established and maximized by addressing challenges including limited acetyl-CoA supply and confined intracellular storage through xylose utilization and two-phase in situ extraction. Furthermore, we demonstrated that xylose metabolism enables efficient co-consumption of acetate under aerobic conditions, arousing an innovative strategy for expanding the capacity of acetyl-CoA supply in Saccharomyces cerevisiae and empowering complete conversion of hemicellulose fractions from switchgrass biomass. This strategy detoxifies acetate as a valuable substrate and facilitates the production of triacetic acid lactone and vitamin A to unprecedented levels reported for S. cerevisiae. Lastly, a xylodextrin-utilizing yeast strain was constructed and its xylodextrin metabolism was improved through rational and evolutionary engineering. The evolved strain with enhanced xylodextrin consumption was further engineered for β-carotene production from Miscanthus autohydrolysates prepared by liquid hot water pretreatment. The engineered yeast strains and strategies described in this study would contribute to economically sustainable conversion of cellulosic carbon sources into valuable natural products.
Issue Date:2020-05-07
Type:Thesis
URI:http://hdl.handle.net/2142/108309
Rights Information:Copyright © 2020 Liang Sun
Date Available in IDEALS:2020-08-27
Date Deposited:2020-05


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